The proposed research is designed to provide core support for histopathology and immunocytochemistry. Brains will be subjected to a battery of staining procedures and morphological analyses. Neuritic plaques, other amyloid deposits and neurofibrillary tangles will initially be visualized by the Rosenwald methods. Alzheimer's disease-related antigens will be localized by immunocytochemistry. The antigens to be examined include: Beta/A4. amyloid precursor protein, paired helical filament, Alz 50, presenilin, GFAP, OX-40, ubiquitin, synaptophysin, spinophilin and protein phosphatase-1. Synaptophysin will be used to immunolabel and quantify axon terminals while spinophilin and protein phosphatase-1 will be used to quantify dendritic spines. The disector technique will be used to quantify neuronal density in the hippocampus. Vascular amyloid deposits will also be analyzed quantitatively. Amyloid deposits will be characterized by electron microscopy. All results will be correlated with those from biochemical studies. The characterization of markers for Alzheimer's disease or of pathology germane to Alzheimer's disease in transgenic mice would guide biochemical studies, lend additional rigor to biochemical results, identify similarities between the transgenic mice and Alzheimer pathology, and provide on measure of the effect of specific constructs on amyloid deposition.